Friday, February 25, 2011

Lesson learned: Outsource but remain in control!

By Dr. Ray Nims

In a previous posting, we described the responsibilities of the contract giver (contractee) and the contract acceptor (contractor) in outsourced pharmaceutical quality control testing. Our blog title: "Outsource it, and fuggedaboutit?" somewhat facetiously suggested that the outsourcing of quality control testing does not transfer quality control responsibility from the contract giver to the contract acceptor.

Elizabeth Meyers and I expanded upon this theme in a recent article in BioProcess International. Our conclusion in that article was more direct: “The use, by a pharma organization, of a contract testing lab to fulfill some or all of its Quality Control testing obligations does not absolve the contractee of its overall Quality responsibility of ensuring the safety, purity, identity, efficacy, and potency of its products.”

This point was illustrated nicely in a recent warning letter published on the FDA Website. The name of the firm involved is not important to this discussion. Among the other findings was the following:

“Your firm failed to properly evaluate a contract laboratory to ensure GMP compliance of operations occurring at the contract site.”

The FDA then provided the following detail: "...we are concerned about your firm’s fundamental understanding of what is required by your Quality Unit and the regulatory expectations for a firm that enters into agreements with contract testing laboratories. Although you have agreements with other firms that may delineate specific responsibilities to each party, you are ultimately responsible for the quality of your products and the reliability of test results. Regardless of who tests your products or the agreements in place, you are required to manufacture these products in accordance with section 501(a)(2)(B) of the Act to assure their identity, strength, quality, purity, and safety."

The take-home message from this is that in the outsourcing of quality control testing, responsibility for the outsourced testing is retained by the contract giver. Responsibilities of the contract giver include the following: selecting and qualifying the contract lab, ensuring the suitability of methods used (through qualification, transfer, verification, or validation); putting in place a Quality and business agreement; scheduling and submitting samples (including communicating expectations for sample results); providing in-life guidance; and monitoring of contract lab performance.

There is no denying that fulfilling these responsibilities requires a significant and ongoing effort on the part of the contract giver. In this respect, outsourcing of quality control testing is not so different from doing that testing in-house.

Wednesday, February 16, 2011

What's up with USP Chapter 1050?

by Dr. Ray Nims

United States Pharmacopeia (USP) general chapter <1050> Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin originally appeared in supplement 10 to USP23-NF18 in May 1999 and was at that time essentially a verbatim adoption of the International Conference of Harmonization (ICH) Guideline Q5A (R1) having the same title.

The chapter describes the methods of evaluating the viral safety of biotechnology pharmaceutical products that are manufactured using cell lines of human or animal origin.

In 2006, an ad hoc advisory panel was assembled by the USP and tasked with revision of this chapter. The goals were to update the chapter and, more specifically, to add greater detail in the viral clearance validation section. The hope was that a user following the recommendations set forth in the general chapter would have greater confidence that viral clearance validation data generated would prove acceptable to the regulatory agencies.

The organization of the revised chapter <1050> was not changed. It comprised the following main sections: 1) Introduction; 2)Potential sources of viral contamination; 3) Cell line qualification: testing for viruses; 4) Testing for viruses in unprocessed bulk; 5) Rationale and action plan for viral clearance studies and viruses tests on purified bulk; and 6) Evaluation and characterization of viral clearance procedures. The changes proposed for the initial 5 sections were minor and primarily reflected attempts to update the chapter and to align the chapter more closely with FDA guidance documents. The most extensive changes were to section 6, in keeping with the goals described above.

The revised chapter was published for public comment in Pharmacopeial Forum 36(3) in the fall of 2010. Comments received as a result of the public review apparently suggested that a more extensive update of the chapter was warranted. At any rate, the revised chapter was not made effective during the USP’s 2005-2010 revision cycle. A new ad hoc advisory panel now being assembled as part of USP's 2010-2015 revision cycle will take over the responsibility for moving the revision of this chapter forward.